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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

doubt that the intensely dysphoric withdrawal syndrome plays an important
role in maintaining episodes of opioid use, but opioid dependence, and
relapse that occurs long after withdrawal cannot be explained solely on this
basis (Koob & Bloom, 1988). Currently, long-term adaptations in neural
systems are also thought to play an important role in dependence and relapse.
In conclusion, the data show complex and broad changes of the
endogenous opioid system following repeated stimulation of mu receptors
by opioids. The precise consequences of those changes remain unclear, but
it is likely that the long-term dysregulation of the opioid system influences
stress responses and drug-taking behaviour.

Neurobiological adaptations to prolonged use
Adaptations following chronic drug exposure extend well beyond reward
circuits to other brain areas, notably those involved in learning and stress
responses. Important regions are the amygdala, hippocampus and cerebral
cortex, which are all connected to the nucleus accumbens. All these areas
express opioid receptors and peptides, and the overall distribution of opioid
peptide-expressing cells in neural circuits of dependence has been reviewed
(Nestler, 2001; Koob & Nestler, 1997).
Repeated exposure to opioids induces drastic and perhaps irreversible
modifications in the brain. Hallmarks of adaptations to chronic opioid use
are tolerance, defined as a reduced sensitivity to the drug effects and generally
referring to attenuation of analgesic efficacy. Drug craving and the
physiological manifestations of drug withdrawal are also indications of long-
term neuroadaptations. These phenomena are a consequence of sustained
mu receptor stimulation by opiate drugs inducing neurochemical adaptations
in opioid receptor-bearing neurons (Kieffer & Evans, 2002).

Pharmacological treatment of opioid dependence

Treatment of heroin dependence has been quite successful because of
substitution therapy and methadone maintenance treatment in particular
(see Box 4.1). Methadone is a synthetic opioid agonist that acts on the same
receptors as opiate drugs, and therefore blocks the effects of heroin,
eliminates withdrawal symptoms, and reduces craving. When properly used,
methadone is non-sedating, non-intoxicating and does not interfere with
regular activities. The medication is taken orally, and it suppresses opioid
withdrawal for 24 hours. There is no cognitive blunting. Its most important
feature is to relieve the craving associated with heroin dependence, thereby
reducing relapse. Methadone maintenance treatment is safe, and very
effective in helping people to stop taking heroin, especially when combined
with behavioural therapies or counselling and other supportive services.
Methadone maintenance treatment can also reduce the risk of contracting
and transmitting HIV, tuberculosis and hepatitis (Krambeer et al., 2001).

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